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1.
Antic, Darko, Milic, Natasa, Chatzikonstantinou, Thomas, Scarfò, Lydia, Otasevic, Vladimir, Rajovic, Nina, Allsup, David, Cabrero, Alejandro Alonso, Andres, Martin, Gonzales, Monica Baile, Capasso, Antonella, Collado, Rosa, Cordoba, Raul, Cuéllar-García, Carolina, Correa, Juan Gonzalo, De Paoli, Lorenzo, De Paolis, Maria Rosaria, Poeta, Giovanni Del, Dimou, Maria, Doubek, Michael, Efstathopoulou, Maria, El-Ashwah, Shaimaa, Enrico, Alicia, Espinet, Blanca, Farina, Lucia, Ferrari, Angela, Foglietta, Myriam, Lopez-Garcia, Alberto, García-Marco, José, García-Serra, Rocío, Gentile, Massimo, Gimeno, Eva, Silva, Maria Gomes, Gutwein, Odit, Hakobyan, Yervand, Herishanu, Yair, Hernández-Rivas, José Ángel, Herold, Tobias, Itchaki, Gilad, Jaksic, Ozren, Janssens, Ann, Kalashnikova, Оlga, Kalicińska, Elżbieta, Kater, Arnon, Kersting, Sabina, Koren-Michowitz, Maya, Gomez, Jorge Labrador, Lad, Deepesh, Laurenti, Luca, Fresa, Alberto, Levin, Mark-David, Bastida, Carlota Mayor, Malerba, Lara, Marasca, Roberto, Marchetti, Monia, Marquet, Juan, Mihaljevic, Biljana, Milosevic, Ivana, Mirás, Fatima, Morawska, Marta, Motta, Marina, Munir, Talha, Murru, Roberta, Nunes, Raquel, Olivieri, Jacopo, Pavlovsky, Miguel Arturo, Piskunova, Inga, Popov, Viola Maria, Quaglia, Francesca Maria, Quaresmini, Giulia, Reda, Gianluigi, Rigolin, Gian Matteo, Shrestha, Amit, Šimkovič, Martin, Smirnova, Svetlana, Špaček, Martin, Sportoletti, Paolo, Stanca, Oana, Stavroyianni, Niki, Raa, Doreen Te, Tomic, Kristina, Tonino, Sanne, Trentin, Livio, Spek, Ellen Der, Gelder, Michel, Varettoni, Marzia, Visentin, Andrea, Vitale, Candida, Vukovic, Vojin, Wasik-Szczepanek, Ewa, Wróbel, Tomasz, Segundo, Lucrecia Yáñez San, Yassin, Mohamed, Coscia, Marta, Rambaldi, Alessandro, Montserrat, Emili, Foà, Robin, Cuneo, Antonio, Carrier, Marc, Ghia, Paolo, Stamatopoulos, Kostas.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334383

ABSTRACT

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. In this retrospective multicenter study, conducted by ERIC, the European Research Initiative on CLL, we assessed the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: : The study included patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. Results: : A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 518 were defined as having severe COVID: 162 were admitted to the ICU while 356 received oxygen supplementation outside the ICU. Most patients (90%) were receiving thromboprophylaxis. During COVID-19 treatment, 8.8% developed a thromboembolic event, while 4.8% experienced bleeding. Thrombosis developed in 20.5% of patients who were not receiving thromboprophylaxis, but only in 8.1% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (11.1% vs. 4.2%, respectively) and in elderly. In multivariate analysis, peak D-dimer level was a poor prognostic factor for thrombosis occurrence (OR=1.020, 95%CI 1.006‒1.033), while thromboprophylaxis use was protective (OR=0.194, 95%CI 0.061‒0.614). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR=1.055, 95%CI 1.013-1.103 and OR=2.490, 95%CI 1.044-5.935, respectively). Conclusions: : Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323357

ABSTRACT

The discovery and the introduction of different vaccines in the therapeutic armamentarium against SARS-CoV-2 represents a big hope in the fight against the pandemic. However, safety of SARS-CoV-2 vaccination is continuously monitored for the emergence of potential new side effects, such as recently reported thrombotic events, after the use of certain types of vaccines. In this context, we report a case of 31-year-old woman who developed immune thrombocytopenia (ITP) after 3 weeks from receiving SARS-CoV-2 vaccine. She developed significant widespread petechiae and gum bleeding, with severe thrombocytopenia documented at her hemogram. Over a 10-day period, thrombocytopenia was treated first with high dose corticosteroids, intravenous immunoglobulin and platelet transfusions, without a platelet response. Two days later, she received the TPO-mimetic and after three days, his platelet count began to rise reaching the normal range 18 days from her admission to our Hematology department. These findings cannot actually elucidate if vaccination was causal or coincidental effect of ITP, but further highlights the need of additional pharmacovigilance studies to empower SARS-CoV2 vaccine efficacy.

3.
IDCases ; 27: e01411, 2022.
Article in English | MEDLINE | ID: covidwho-1652573

ABSTRACT

Background: The multisystem inflammatory syndrome (MIS) is a rare and sometime life-threatening post-infectious complication of coronavirus disease 2019 (Covid-19) in children and adults. To date, only a very few reports have associated such systemic reaction with SARS-CoV-2 vaccination. Case report: we describe a case that resembled MIS, in a 46-year-old White man, 12 days after vaccination with Ad26. COV2. S vaccine (Johnson &Johnson/Janssen), a recombinant adenovirus serotype 26 vector encoding the SARS-CoV-2 spike glycoprotein. The patient experienced high grade fever, cutaneous rash, severe weakness, pericardial effusion and raised inflammatory markers, which met the criteria for definition of MIS. The symptoms improved with steroidal therapy. Conclusions: Our case suggests that MIS could occur after SARS-CoV-2 vaccination.

4.
Am J Hematol ; 97(2): E75-E78, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1565162
5.
Leukemia ; 35(12): 3444-3454, 2021 12.
Article in English | MEDLINE | ID: covidwho-1493064

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41-0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02-1.04; HR = 1.79, 95% CI:1.04-3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.


Subject(s)
COVID-19/complications , COVID-19/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , COVID-19/diagnosis , COVID-19/virology , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Leukemia, Lymphocytic, Chronic, B-Cell/virology , Mortality , Prognosis , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
6.
Microorganisms ; 9(1)2021 Jan 03.
Article in English | MEDLINE | ID: covidwho-1389447

ABSTRACT

The expression rate of SARS-CoV-2 entry genes, angiotensin-converting enzyme 2 (ACE2), the main viral receptor and the proteases, furin and transmembrane serine protease 2 (TMPRSS2) in cystic fibrosis (CF) individuals is poorly known. Hence, we examined their levels in upper respiratory samples of CF patients (n = 46) and healthy controls (n = 45). Moreover, we sought to understand the interplay of type I interferon (IFN-I) with ACE2, furin and TMPRSS2 by evaluating their gene expression with respect to ISG15, a well-known marker of IFN activation, in upper respiratory samples and after ex vivo IFNß exposure. Lower ACE2 levels and trends toward the reduction of furin and TMPRSS2 were found in CF patients compared with the healthy controls; decreased ACE2 amounts were also detected in CF individuals with pancreatic insufficiency and in those receiving inhaled antibiotics. Moreover, there was a strong positive correlation between ISG15 and ACE2 levels. However, after ex vivo IFNß stimulation of nasopharyngeal cells, the truncated isoform (dACE2), recently demonstrated as the IFN stimulated one with respect to the full-length isoform (flACE2), slightly augmented in cells from CF patients whereas in those from healthy donors, dACE2 levels showed variable levels of upregulation. An altered expression of SARS-COV-2 entry genes and a poor responsiveness of dACE2 to IFN-I stimulation might be crucial in the diffusion of SARS-CoV-2 infection in CF.

8.
Roeker, Lindsey E.; Scarfo, Lydia, Chatzikonstantinou, Thomas, Abrisqueta, Pau, Eyre, Toby A.; Cordoba, Raul, Muntañola Prat, Ana, Villacampa, Guillermo, Leslie, Lori A.; Koropsak, Michael, Quaresmini, Giulia, Allan, John N.; Furman, Richard R.; Bhavsar, Erica B.; Pagel, John M.; Hernandez-Rivas, Jose Angel, Patel, Krish, Motta, Marina, Bailey, Neil, Miras, Fatima, Lamanna, Nicole, Alonso, Rosalia, Osorio-Prendes, Santiago, Vitale, Candida, Kamdar, Manali, Baltasar, Patricia, Österborg, Anders, Hanson, Lotta, Baile, Mónica, Rodríguez-Hernández, Ines, Valenciano, Susana, Popov, Viola Maria, Barez Garcia, Abelardo, Alfayate, Ana, Oliveira, Ana C.; Eichhorst, Barbara, Quaglia, Francesca M.; Reda, Gianluigi, Lopez Jimenez, Javier, Varettoni, Marzia, Marchetti, Monia, Romero, Pilar, Riaza Grau, Rosalía, Munir, Talha, Zabalza, Amaya, Janssens, Ann, Niemann, Carsten U.; Perini, Guilherme Fleury, Delgado, Julio, Yanez San Segundo, Lucrecia, Gómez Roncero, Ma Isabel, Wilson, Matthew, Patten, Piers, Marasca, Roberto, Iyengar, Sunil, Seddon, Amanda, Torres, Ana, Ferrari, Angela, Cuéllar-García, Carolina, Wojenski, Daniel, El-Sharkawi, Dima, Itchaki, Gilad, Parry, Helen, Mateos-Mazón, Juan José, Martinez-Calle, Nicolas, Ma, Shuo, Naya, Daniel, Van Der Spek, Ellen, Seymour, Erlene K.; Gimeno Vázquez, Eva, Rigolin, Gian Matteo, Mauro, Francesca Romana, Walter, Harriet S.; Labrador, Jorge, De Paoli, Lorenzo, Laurenti, Luca, Ruiz, Elena, Levin, Mark-David, Šimkovič, Martin, Špaček, Martin, Andreu, Rafa, Walewska, Renata, Perez-Gonzalez, Sonia, Sundaram, Suchitra, Wiestner, Adrian, Cuesta, Amalia, Broom, Angus, Kater, Arnon P.; Muiña, Begoña, Velasquez, César A.; Ujjani, Chaitra S.; Seri, Cristina, Antic, Darko, Bron, Dominique, Vandenberghe, Elisabeth, Chong, Elise A.; Lista, Enrico, García, Fiz Campoy, Del Poeta, Giovanni, Ahn, Inhye, Pu, Jeffrey J.; Brown, Jennifer R.; Soler Campos, Juan Alfonso, Malerba, Lara, Trentin, Livio, Orsucci, Lorella, Farina, Lucia, Villalon, Lucia, Vidal, Maria Jesus, Sanchez, Maria Jose, Terol, Maria Jose, De Paolis, Maria Rosaria, Gentile, Massimo, Davids, Matthew S.; Shadman, Mazyar, Yassin, Mohamed A.; Foglietta, Myriam, Jaksic, Ozren, Sportoletti, Paolo, Barr, Paul M.; Ramos, Rafael, Santiago, Raquel, Ruchlemer, Rosa, Kersting, Sabina, Huntington, Scott F.; Herold, Tobias, Herishanu, Yair, Thompson, Meghan C.; Lebowitz, Sonia, Ryan, Christine, Jacobs, Ryan W.; Portell, Craig A.; Isaac, Krista, Rambaldi, Alessandro, Nabhan, Chadi, Brander, Danielle M.; Montserrat, Emili, Rossi, Giuseppe, Garcia-Marco, Jose A.; Coscia, Marta, Malakhov, Nikita, Fernandez-Escalada, Noemi, Skånland, Sigrid Strand, Coombs, Callie C.; Ghione, Paola, Schuster, Stephen J.; Foà, Robin, Cuneo, Antonio, Bosch, Francesc, Stamatopoulos, Kostas, Ghia, Paolo, Mato, Anthony R.; Patel, Meera.
Blood ; 136(Supplement 1):45-49, 2020.
Article in English | PMC | ID: covidwho-1338959

ABSTRACT

Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020;Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we partnered in a worldwide effort to describe the clinical experience and validate predictors of survival, including potential treatment effects.Methods: This international collaboration represents a partnership between investigators at 141 centers. Data are presented in two cohorts. Cohort 1 (Co1) includes pts captured through efforts by European Research Initiative on CLL (ERIC), Italian CAMPUS CLL Program, and Grupo Español de Leucemia Linfática Crónica. The validation cohort, Cohort 2 (Co2), includes pts from US (66%), UK (23%), EU (7%), and other countries (4%). There is no overlap in cases between cohorts.CLL pts were included if COVID-19 was diagnosed by PCR detection of SARS-CoV-2 and they required inpatient hospitalization. Data were collected retrospectively 2/2020 - 5/2020 using standardized case report forms. Baseline characteristics, preexisting comorbidities (including cumulative illness rating scale (CIRS) score ≥6 vs. <6), CLL treatment history, details regarding COVID-19 course, management, and therapy, and vital status were collected.The primary endpoint of this study was to estimate the case fatality rate (CFR), defined as the proportion of pts who died among all pts hospitalized with COVID-19. Chi-squared test was used to compare frequencies;univariable and multivariable analyses utilized Cox regression. Predictors of inferior OS in both Co1 and Co2 were included in multivariable analyses. Kaplan-Meier method was used to estimate overall survival (OS) from time of COVID-19 diagnosis (dx).Results: 411 hospitalized, COVID-19 positive CLL pts were analyzed (Co1 n=281, Co2 n=130). Table 1 describes baseline characteristics. At COVID-19 dx, median age was 72 in Co1 (range 37-94) and 68 in Co2 (range 41-98);31% (Co1) and 45% (Co2) had CIRS ≥6. In Co1, 48% were treatment-naïve and 26% were receiving CLL-directed therapy at COVID-19 dx (66% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.6% chemo/chemoimmunotherapy (CIT), 1.4% PI3Ki, 4% other). In Co2, 36% were never treated and 49% were receiving CLL-directed therapy (65% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.4% multi-novel agent combinations, 1.6% CIT, 1.6% PI3Ki, 1.6% anti-CD20 monotherapy, 1.6% other). Most pts receiving CLL-directed therapy had it held at COVID-19 diagnosis (93% in Co1 and 81% in Co2).Frequency of most COVID-19 symptoms/laboratory abnormalities were similar in the two cohorts including fever (88% in both), lymphocytosis (ALC ≥30 x 109/L;27% vs. 21%), and lymphocytopenia (ALC <1.0 x 109/L;18% vs. 28%), while others varied between Co1 and Co2 (p<0.0001), including cough (61% vs. 93%), dyspnea (60% vs. 84%), fatigue (13% vs. 77%).Median follow-up was 24 days (range 2-86) in Co1 and 17 days (1-43) in Co2. CFRs were similar in Co1 and Co2, 30% and 34% (p=0.45). 54% and 43% were discharged while 16% and 23% remained admitted at last follow-up in Co1 and Co2, respectively. The proportion of pts requiring supplemental oxygen was similar (89% vs. 92%) while rate of ICU admission was higher in Co2 (20% vs. 48%, p<0.0001). Figure 1 depicts OS in each cohort. Univariable analyses demonstrated that age and CIRS ≥6 significantly predicted inferior OS in both cohorts, while only age remained an independent predictor of inferior OS in multivariable analyses (Table 2). Prior treatment for CLL (vs. observation) predicted inferior OS in Co1 but not Co2.Conclusions : In the largest cancer dx-specific cohort reported, pts with CLL hospitalized for COVID-19 had a CFR of 30-34%. Advanced patient age at COVID-19 diagnosis was an independent predictor of OS in two large cohorts. This CFR will serve as a benchmark for mortality for future outcomes studies, including thera eutic interventions for COVID-19 in this population. The effect of CLL treatment on OS was inconsistent across cohorts;COVID-19 may be severe regardless of treatment status. While there were no significant differences in distribution of current lines of therapy between cohorts, prior chemo exposure was more common in Co1 vs. Co2, which may account for difference in OS. Extended follow-up will be presented.

10.
J Med Virol ; 93(7): 4399-4404, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1263104

ABSTRACT

The role of viruses in community acquired pneumonia (CAP) has been largely underestimated in the pre-coronavirus disease 2019 age. However, during flu seasonal early identification of viral infection in CAP is crucial to guide treatment and in-hospital management. Though recommended, the routine use of nasopharyngeal swab (NPS) to detect viral infection has been poorly scaled-up, especially in the emergency department (ED). This study sought to assess the prevalence and associated clinical outcomes of viral infections in patients with CAP during peak flu season. In this retrospective, observational study adults presenting at the ED of our hospital (Rome, Italy) with CAP from January 15th to February 22th, 2019 were enrolled. Each patient was tested on admission with Influenza rapid test and real time multiplex assay. Seventy five consecutive patients were enrolled. 30.7% (n = 23) tested positive for viral infection. Of these, 52.1% (n = 12) were H1N1/FluA. 10 patients had multiple virus co-infections. CAP with viral infection did not differ for any demographic, clinic and laboratory features by the exception of CCI and CURB-65. All intra-ED deaths and mechanical ventilations were recorded among CAP with viral infection. Testing only patients with CURB-65 score ≥2, 10 out of 12 cases of H1N1/FluA would have been detected saving up to 40% tests. Viral infection occurred in one-third of CAP during flu seasonal peak 2019. Since not otherwise distinguishable, NPS is so far the only reliable mean to identify CAP with viral infection. Testing only patients with moderate/severe CAP significantly minimize the number of tests.


Subject(s)
Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Pneumonia/virology , Aged , COVID-19/epidemiology , Coinfection/virology , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Italy/epidemiology , Male , Prevalence , Retrospective Studies , SARS-CoV-2/isolation & purification
11.
J Med Virol ; 93(2): 886-891, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196414

ABSTRACT

Italy was one of the most affected nations by coronavirus disease 2019 outside China. The infections, initially limited to Northern Italy, spread to all other Italian regions. This study aims to provide a snapshot of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemiology based on a single-center laboratory experience in Rome. The study retrospectively included 6565 subjects tested for SARS-CoV-2 at the Laboratory of Virology of Sapienza University Hospital in Rome from 6 March to 4 May. A total of 9995 clinical specimens were analyzed, including nasopharyngeal swabs, bronchoalveolar lavage fluids, gargle lavages, stools, pleural fluids, and cerebrospinal fluids. Positivity to SARS-CoV-2 was detected in 8% (527/6565) of individuals, increased with age, and was higher in male patients (P < .001). The number of new confirmed cases reached a peak on 18 March and then decreased. The virus was detected in respiratory samples, in stool and in pleural fluids, while none of gargle lavage or cerebrospinal fluid samples gave a positive result. This analysis allowed to gather comprehensive information on SARS-CoV-2 epidemiology in our area, highlighting positivity variations over time and in different sex and age group and the need for a continuous surveillance of the infection, mostly because the pandemic evolution remains unknown.


Subject(s)
COVID-19 , Pandemics , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/virology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Child , Child, Preschool , Feces/virology , Female , Hospitals, University , Humans , Infant , Infant, Newborn , Laboratories , Male , Middle Aged , Nasopharynx/virology , Pleural Effusion/virology , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Rome/epidemiology , SARS-CoV-2/genetics , Severity of Illness Index
12.
J Med Virol ; 93(7): 4399-4404, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1156883

ABSTRACT

The role of viruses in community acquired pneumonia (CAP) has been largely underestimated in the pre-coronavirus disease 2019 age. However, during flu seasonal early identification of viral infection in CAP is crucial to guide treatment and in-hospital management. Though recommended, the routine use of nasopharyngeal swab (NPS) to detect viral infection has been poorly scaled-up, especially in the emergency department (ED). This study sought to assess the prevalence and associated clinical outcomes of viral infections in patients with CAP during peak flu season. In this retrospective, observational study adults presenting at the ED of our hospital (Rome, Italy) with CAP from January 15th to February 22th, 2019 were enrolled. Each patient was tested on admission with Influenza rapid test and real time multiplex assay. Seventy five consecutive patients were enrolled. 30.7% (n = 23) tested positive for viral infection. Of these, 52.1% (n = 12) were H1N1/FluA. 10 patients had multiple virus co-infections. CAP with viral infection did not differ for any demographic, clinic and laboratory features by the exception of CCI and CURB-65. All intra-ED deaths and mechanical ventilations were recorded among CAP with viral infection. Testing only patients with CURB-65 score ≥2, 10 out of 12 cases of H1N1/FluA would have been detected saving up to 40% tests. Viral infection occurred in one-third of CAP during flu seasonal peak 2019. Since not otherwise distinguishable, NPS is so far the only reliable mean to identify CAP with viral infection. Testing only patients with moderate/severe CAP significantly minimize the number of tests.


Subject(s)
Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Pneumonia/virology , Aged , COVID-19/epidemiology , Coinfection/virology , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Italy/epidemiology , Male , Prevalence , Retrospective Studies , SARS-CoV-2/isolation & purification
13.
Microorganisms ; 9(1)2021 Jan 03.
Article in English | MEDLINE | ID: covidwho-1011585

ABSTRACT

The expression rate of SARS-CoV-2 entry genes, angiotensin-converting enzyme 2 (ACE2), the main viral receptor and the proteases, furin and transmembrane serine protease 2 (TMPRSS2) in cystic fibrosis (CF) individuals is poorly known. Hence, we examined their levels in upper respiratory samples of CF patients (n = 46) and healthy controls (n = 45). Moreover, we sought to understand the interplay of type I interferon (IFN-I) with ACE2, furin and TMPRSS2 by evaluating their gene expression with respect to ISG15, a well-known marker of IFN activation, in upper respiratory samples and after ex vivo IFNß exposure. Lower ACE2 levels and trends toward the reduction of furin and TMPRSS2 were found in CF patients compared with the healthy controls; decreased ACE2 amounts were also detected in CF individuals with pancreatic insufficiency and in those receiving inhaled antibiotics. Moreover, there was a strong positive correlation between ISG15 and ACE2 levels. However, after ex vivo IFNß stimulation of nasopharyngeal cells, the truncated isoform (dACE2), recently demonstrated as the IFN stimulated one with respect to the full-length isoform (flACE2), slightly augmented in cells from CF patients whereas in those from healthy donors, dACE2 levels showed variable levels of upregulation. An altered expression of SARS-COV-2 entry genes and a poor responsiveness of dACE2 to IFN-I stimulation might be crucial in the diffusion of SARS-CoV-2 infection in CF.

14.
Virus Res ; 295: 198283, 2021 04 02.
Article in English | MEDLINE | ID: covidwho-1009920

ABSTRACT

The natural course of type I and III interferon (IFN) response in the respiratory tract of COVID-19 patients needs to be better defined. We showed that type I/III IFNs, IFN-regulatory factor 7 (IRF7), and IFN stimulated genes (ISGs), are highly expressed in the oropharyngeal cells of SARS-CoV-2 positive patients compared to healthy controls. Notably, the subgroup of critically-ill patients that required invasive mechanical ventilation had a general decrease in expression of IFN/ISG genes. Heterogeneous patterns of IFN-I/III response in the respiratory tract of COVID-19 patients may be associated to COVID-19 severity.


Subject(s)
COVID-19/immunology , Interferon Type I/genetics , Interferons/genetics , Oropharynx/immunology , SARS-CoV-2 , Adult , Aged , Female , Humans , Male , Middle Aged , Severity of Illness Index
15.
J Clin Virol ; 133: 104660, 2020 12.
Article in English | MEDLINE | ID: covidwho-856843

ABSTRACT

BACKGROUND: The detection of a low amount of viral RNA is crucial to identify a SARS-CoV-2 positive individual harboring a low level of virus, especially during the convalescent period. However, the detection of one gene at high Cycle threshold (Ct) has to be interpreted with caution. In this study we address this specific issue and report our real-life experience. STUDY DESIGN: A total of 1639 nasopharyngeal swabs (NPS) were analyzed with Xpert® Xpress SARS-CoV-2. Positive samples showing high Ct values (Ct>35) were concentrated by centrifugation and re-tested with Cepheid or other methods (RealStar SARS-CoV2 RT-PCR, Altona Diagnostics; GeneFinder COVID-19 Plus RealAmp Kit, Elitech). RESULTS: 1599 (97.5%) negative samples, 36 (2.3%) positive samples and 4 (0.2%) presumptive positive samples were detected. In 17 out of 36 positive patients, very low viral RNA copies were suspected since positivity was detected at high Ct. We confirmed positivity for patients who showed both E and N genes detected and for patients with only N detected but with Ct <39. On the contrary, samples with only gene N detected with Ct values >39 were found negative. NPS taken 24 hours after the first collection confirmed the negativity of the 12 samples. Clinical data sustained these results since only 2 of these 12 patients showed COVID-19-like symptoms. CONCLUSIONS: These data support our consideration that detection of the N2 gene at high Ct needs to be interpreted with caution, suggesting that collaboration between virologists and clinicians is important for better understanding of results.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/genetics , False Positive Reactions , RNA, Viral/analysis , Humans , Nasopharynx/virology , Phosphoproteins/genetics , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
16.
Leukemia ; 34(9): 2354-2363, 2020 09.
Article in English | MEDLINE | ID: covidwho-638239

ABSTRACT

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pneumonia, Viral/pathology , Adenine/analogs & derivatives , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , COVID-19 , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Male , Middle Aged , Pandemics , Piperidines , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Prognosis , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Surveys and Questionnaires
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